ConditionBrain & nerves
Paraproteinemic Neuropathy
Paraproteinemic neuropathy is peripheral nerve damage that occurs alongside a paraprotein (monoclonal protein), an abnormal antibody made by a single clone of plasma cells or B cells. It usually affects people over 50 and causes numbness, tingling, unsteadiness and sometimes weakness, starting in the feet. Most cases involve MGUS, a common benign condition, but some are linked to anti-MAG antibodies, POEMS syndrome, amyloidosis, myeloma or Waldenström macroglobulinemia. Treatment depends on the type and on the underlying blood disorder.
Also called: Paraprotein-associated neuropathy, neuropathy with monoclonal gammopathy, MGUS neuropathy, anti-MAG neuropathy
At a glance
- What it is
- Peripheral neuropathy occurring with a monoclonal protein in the blood.
- Who gets it
- Mostly adults over 50, more often men.
- Main types
- IgM with anti-MAG antibodies, IgG or IgA MGUS neuropathy, POEMS syndrome, amyloid neuropathy, and neuropathy with myeloma or Waldenström.
- Symptoms
- Numbness, tingling, unsteady walking, hand tremor, weakness, sometimes pain or autonomic problems.
- Treatment
- Depends on type: immune therapy, rituximab, or treating the plasma cell disorder.
When to get help
See a doctor within a day or two
- Weakness that worsens over days to weeks, or difficulty walking or using the hands
- Neuropathy with weight loss, bone pain, swelling of the legs, skin darkening or thickening, or new heart or kidney problems
- Dizziness on standing, diarrhea, or erectile dysfunction developing with painful feet (possible amyloidosis)
Book a routine appointment
- Numbness, tingling or unsteadiness in the feet that is gradually spreading
- A paraprotein or MGUS found on blood tests, with any nerve symptoms
- A hand tremor with numb feet and poor balance after age 50
What a paraprotein is
Plasma cells normally make many different antibodies (immunoglobulins). When one clone of cells expands, it produces large amounts of one identical antibody, called a monoclonal protein, M-protein or paraprotein. Paraproteins are named by their type: IgM, IgG or IgA, with kappa or lambda light chains.
MGUS (monoclonal gammopathy of undetermined significance) is the most common cause, found in about 3 in 100 people over 50. MGUS itself is not cancer, but it carries a small yearly risk (about 1 in 100) of progressing to a blood cancer. In some people, the paraprotein or the cells making it damage nerves.
Types of paraproteinemic neuropathy
| Type | Typical features | Treatment approach |
|---|---|---|
| IgM with anti-MAG antibodies | Slowly progressive numbness and poor balance in the feet, hand tremor, mild weakness, mostly men over 60 | Rituximab if symptoms are significant or progressing |
| IgM without anti-MAG | Variable, often sensory | Tailored, sometimes rituximab |
| IgG or IgA MGUS | Can resemble chronic inflammatory demyelinating polyneuropathy (CIDP) | Treated like CIDP: IV immunoglobulin, steroids, plasma exchange |
| POEMS syndrome | Progressive weakness, lambda light chain, organ enlargement, skin changes, swelling, very high VEGF | Treat the plasma cell disorder: radiation, chemotherapy, stem cell transplant |
| AL amyloidosis | Painful, burning feet, autonomic problems, carpal tunnel syndrome, heart and kidney involvement | Chemotherapy targeting the plasma cells |
| Multiple myeloma or Waldenström macroglobulinemia | Neuropathy from the disease or its treatment, sometimes from anti-MAG or amyloid | Treat the cancer |
| Cryoglobulinemia | Painful neuropathy, rash, joint pain, worse in cold | Treat the cause (often hepatitis C), immune therapy |
POEMS stands for Polyneuropathy, Organomegaly (enlarged organs), Endocrinopathy (hormone problems), Monoclonal protein and Skin changes. It is rare but important, because it is often misdiagnosed as CIDP and responds well to treatment of the plasma cells.
Symptoms
- numbness, tingling or pins and needles starting in the toes and feet and spreading upward
- loss of position sense, causing unsteadiness, especially in the dark (sensory ataxia)
- hand tremor, typical of anti-MAG neuropathy
- muscle weakness, more prominent in CIDP-like and POEMS neuropathy
- burning pain in the feet, especially with amyloidosis
- autonomic symptoms in amyloidosis: dizziness on standing, diarrhea or constipation, erectile dysfunction
Diagnosis
- Blood and urine tests: serum protein electrophoresis with immunofixation, serum free light chains, and urine studies to detect and type the paraprotein
- anti-MAG antibody testing when an IgM paraprotein is present
- VEGF level if POEMS is suspected
- nerve conduction studies and EMG to show whether the neuropathy is demyelinating or axonal
- hematology assessment: bone marrow biopsy, skeletal imaging (low-dose CT or PET-CT), kidney function and calcium
- tests for amyloid: fat pad or nerve biopsy, heart imaging
- exclusion of other causes: diabetes, B12 deficiency, alcohol, thyroid disease and medicines
Because MGUS is common, a paraprotein may be a coincidental finding in someone whose neuropathy has another cause. Specialists weigh the pattern of symptoms and nerve studies to decide whether they are linked.
Treatment
- Anti-MAG neuropathy: many people have slowly progressive, mainly sensory symptoms and may be monitored. Rituximab is used when symptoms are disabling or worsening.
- IgG or IgA CIDP-like neuropathy: IV or subcutaneous immunoglobulin, steroids or plasma exchange.
- POEMS, amyloidosis, myeloma and Waldenström: treatment of the underlying blood disorder by a hematologist, often leading to gradual nerve improvement.
- Symptom management: physical therapy for balance and strength, walking aids, fall prevention, foot care, and nerve pain medicines.
- Monitoring: regular blood tests to watch the paraprotein and catch progression to a blood cancer early.
Outlook
Outcomes vary by type. Anti-MAG neuropathy usually progresses slowly over many years and many people remain walking independently. CIDP-like neuropathies often respond to immune treatment. POEMS and amyloid neuropathy can improve when the underlying disease is treated early, but nerve recovery is slow.
Frequently asked questions
What is paraproteinemic neuropathy?
It is damage to the peripheral nerves that occurs together with an abnormal antibody (paraprotein) in the blood. The paraprotein is usually from MGUS, a benign condition, but may come from other plasma cell or B-cell disorders.
Can MGUS cause neuropathy?
Yes. MGUS, especially the IgM type, can be associated with neuropathy, sometimes through anti-MAG antibodies that attack nerve myelin. However, MGUS is common, so a doctor must decide whether it is truly the cause of the nerve problem.
What is anti-MAG neuropathy?
It is a slowly progressive neuropathy caused by IgM antibodies against myelin-associated glycoprotein on nerves. It typically causes numb feet, poor balance and hand tremor in men over 60. Rituximab is used when symptoms are significant.
What is POEMS syndrome?
POEMS syndrome is a rare plasma cell disorder causing polyneuropathy, enlarged organs, hormone problems, a monoclonal protein and skin changes. It often causes progressive weakness. Treating the plasma cells with radiation, chemotherapy or stem cell transplant can improve the neuropathy.
How is paraproteinemic neuropathy treated?
Treatment depends on the type. Options include immunoglobulin, steroids or plasma exchange for CIDP-like neuropathy, rituximab for anti-MAG neuropathy, and treatment of the underlying blood disorder for POEMS, amyloidosis, myeloma or Waldenström.
Sources
This guide was written from current patient and clinical guidance, including:
- European Academy of Neurology and Peripheral Nerve Society: Guideline on paraproteinemic demyelinating neuropathies
- International Myeloma Working Group: MGUS definition and risk stratification
- National Organization for Rare Disorders (NORD): POEMS syndrome
- MedlinePlus (US National Library of Medicine): Monoclonal gammopathy of undetermined significance
- National Institute of Neurological Disorders and Stroke (NINDS): Peripheral neuropathy